The role of soluble factors produced by lymphocytes and monocytes in controlling the activation, proliferation and differentiation of lymphocytes participating in immunological functions was studied. Studies were performed with B and T lymphocytes to establish the requirement of various soluble factors (interleukins) in the development of functional lymphocytic populations. B-cells. Purified GO B-cells activated under controlled conditions by anti Mu reagents remain in GO state. However such cells have undergone significant changes since they gained the ability to proliferate in response to soluble mediators. The biochemical changes that occur as a result of stimulating BO B-cells with various agents implicates the turnover of phosphatidylinositol as an early event in B-cell activation. T-cells. The in vitro activation of cytotoxic lymphocyte precursors requires, in addition to IL-2, components present in fetal calf serum (FCS). The active substance(s) from FCS after partial purification display none of the biological properties of the known classical interleukins. The significance of these studies is that soluble factors play an ever increasing critical role in regulating lymphocyte activity. Characterization of these pharmacologically active substances and their role(s) in establishing immune function are imprtant aspects in the understanding of the immune system.